Amelioration of lung reperfusion injury by L- and E- selectin blockade

OBJECTIVE: Reperfusion injury is the main reason for early graft failure after lung transplantation. Inhibition of the adherence of polymorphonuclear leukocytes to activated endothelium by blocking L- and E-selectins (antibody EL-246) could potentially inhibit reperfusion injury. METHODS: Reperfusion injury was induced in a left lung autotransplant model in sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 h in situ at 15 degrees C. After reperfusion right main bronchus and pulmonary artery were occluded leaving the animal dependent on the reperfused lung (control, n = 6). Pulmonary function was assessed by alveolo-arterial oxygen difference (AaDO2) and pulmonary vascular resistance (PVR), the chemiluminescence of isolated neutrophils, as well as the release of beta-N-acetyl-glucosaminidase (beta-NAG) served as indicator of neutrophilic activation. Extravascular lung water was an indicator for pulmonary edema formation. EL-246 group animals (n = 6) were treated additionally with 1 mg/kg BW of EL-246 given prior and during reperfusion. RESULTS: After 3 h of reperfusion five control animals developed alveolar edema compared to one animal in the EL-246 group (P = 0.08). AaDO2 (mm Hg) was significantly higher in the control compared to the EL-246 group (510 +/- 148 vs. 214 +/- 86). PVR (dyn x s x cm(-5)) was significantly increased in the control compared to the EL-246 group (656 +/- 240 vs. 317 +/- 87). Neutrophilic activation was significantly lower in the EL-246 group. Extravascular lung water was significantly lower compared to control (6.88 +/- 1.0 vs. 13.4 +/- 2.8 g/g blood-free lung weight). CONCLUSIONS: Treatment with EL-246 results in improved pulmonary function and less in vivo PMN activation in this experimental model. Further studies are necessary to evaluate the possible role of selectin blockade in amelioration of reperfusion injury in human lung transplantation.

Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.

Complete arterial revascularization in multivessel coronary artery disease with 2 conduits (skeletonized grafts and T grafts)

BACKGROUND: Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis. METHODS AND RESULTS: Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%). CONCLUSIONS: Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.

Haemodynamic and arrhythmic effects of moderately cold (22 degrees C) water immersion and swimming in patients with stable coronary artery disease and heart failure

AIMS: Data on moderately cold water immersion and occurrence of arrhythmias in chronic heart failure (CHF) patients are scarce. METHODS AND RESULTS: We examined 22 male patients, 12 with CHF [mean age 59 years, ejection fraction (EF) 32%, NYHA class II] and 10 patients with stable coronary artery disease (CAD) without CHF (mean age 65 years, EF 52%). Haemodynamic effects of water immersion and swimming in warm (32 degrees C) and moderately cold (22 degrees C) water were measured using an inert gas rebreathing method. The occurrence of arrhythmias during water activities was compared with those measured during a 24 h ECG recording. Rate pressure product during water immersion up to the chest was significantly higher in moderately cold (P = 0.043 in CHF, P = 0.028 in CAD patients) compared with warm water, but not during swimming. Rate pressure product reached 14200 in CAD and 12 400 in CHF patients during swimming. Changes in cardiac index (increase by 5-15%) and oxygen consumption (increase up to 20%) were of similar magnitude in moderately cold and warm water. Premature ventricular contractions (PVCs) increased significantly in moderately cold water from 15 +/- 41 to 76 +/- 163 beats per 30 min in CHF (P = 0.013) but not in CAD patients (20 +/- 33 vs. 42 +/- 125 beats per 30 min, P = 0.480). No ventricular tachycardia was noted. CONCLUSION: Patients with compensated CHF tolerate water immersion and swimming in moderately cold water well. However, the increase in PVCs raises concerns about the potential danger of high-grade ventricular arrhythmias.

Revascularisation of coronary artery disease in patients with diabetes mellitus

Diabetes mellitus is becoming increasingly prevalent and magnifies the risk of cardiovascular complications. Endothelial dysfunction caused by oxidative stress is a hallmark of diabetes and is responsible for the ubiquitous manifestations of vascular disease in diabetics. Compared with non-diabetic patients, coronary artery disease is more severe and the clinical outcome impaired in diabetic patients undergoing revascularisation. Despite these limitations the benefit of revascularisation therapy is particularly pronounced in diabetics. The optimal revascularisation strategy (coronary artery bypass graft surgery versus percutaneous coronary intervention) in diabetic patients with coronary artery disease depends on clinical and anatomical considerations.

Early- and long-term intravascular ultrasound and angiographic findings after bioabsorbable magnesium stent implantation in human coronary arteries

OBJECTIVES: This study aimed to evaluate the degradation rate and long-term vascular responses to the absorbable metal stent (AMS). BACKGROUND: The AMS demonstrated feasibility and safety at 4 months in human coronary arteries. METHODS: The PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting) was a prospective, multicenter clinical trial of 63 patients with coronary artery disease who underwent AMS implantation. Angiography and intravascular ultrasound (IVUS) were conducted immediately after AMS deployment and at 4 months. Eight patients who did not require repeat revascularization at 4 months underwent late angiographic and IVUS follow-up from 12 to 28 months. RESULTS: The AMS was well-expanded upon deployment without immediate recoil. The major contributors for restenosis as detected by IVUS at 4 months were: decrease of external elastic membrane volume (42%), extra-stent neointima (13%), and intra-stent neointima (45%). From 4 months to late follow-up, paired IVUS analysis demonstrated complete stent degradation with durability of the 4-month IVUS indexes. The neointima was reduced by 3.6 +/- 5.2 mm(3), with an increase in the stent cross sectional area of 0.5 +/- 1.0 mm(2) (p = NS). The median in-stent minimal lumen diameter was increased from 1.87 to 2.17 mm at long-term follow-up. The median angiographic late loss was reduced from 0.62 to 0.40 mm by quantitative coronary angiography from 4 months to late follow-up. CONCLUSIONS: Intravascular ultrasound imaging supports the safety profile of AMS with degradation at 4 months and maintains durability of the results without any early or late adverse findings. Slower degradation is warranted to provide sufficient radial force to improve long-term patency rates of the AMS.

Diabetes and acute coronary syndromes

Diabetic patients with acute coronary syndromes (ACSs) are at a high risk for subsequent cardiovascular events but derive, at the same time, greater benefit from evidence-based therapy than non-diabetic individuals. State-of-the-art anti-thrombotic therapy includes a triple anti-platelet combination - aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa receptor inhibitors - and unfractionated heparin or enoxaparin. For low- or medium-risk individuals, a treatment based on aspirin, clopidogrel and bivalirudin is a valuable alternative. Prasugrel, a new and more potent inhibitor of the platelet P2Y(12) receptor, has to be regarded as the most promising anti-thrombotic agent for diabetic patients with ACS. This agent may replace clopidogrel - and possibly GP IIb/IIIa inhibitors - in the future. In addition to aggressive anti-thrombotic therapy, diabetic patients should undergo systematic early invasive angiography if presenting with non-ST-segment elevation ACS, and immediate percutaneous coronary intervention if presenting with ST-segment elevation myocardial infarction. Indeed, the benefit derived from these strategies appears to be more pronounced in the diabetic population than in non-diabetic individuals. Despite the benefit, multiple surveys have demonstrated that, in the setting of ACS, diabetic patients receive evidence-based therapy less frequently than non-diabetic counterparts.

[The role of percutaneus coronary interventions in the treatment of coronary artery disease]

In industrial countries, cardiovascular diseases remain the primary cause of death. This review summarizes the role of percutaneous coronary interventions (PCI) in the treatment of coronary heart disease. Interventional therapy of coronary artery disease was initiated in 1977 with the introduction of balloon angioplasty by Andreas Grüntzig in Zurich. Technical progress since has been related to construction and materials of catheters, but also to digital processing of x-ray imaging. Additional methods - rotablation, atherectomy, laser, intravascular ultrasound, and most importantly stent implantation were developed. Only stents significantly changed the procedure. They are today an integral part of PCI.

Comparison of long versus short ("spot") drug-eluting stenting for long coronary stenoses

We compared spot drug-eluting stenting (DES) to full stent coverage for treatment of long coronary stenoses. Consecutive, consenting patients with a long (>20 mm) coronary lesion of nonuniform severity and indication for percutaneous coronary intervention were randomized to full stent coverage of the atherosclerotic lesion with multiple, overlapping stenting (full DES group, n = 90) or spot stenting of hemodynamically significant parts of the lesion only (defined as diameter stenosis >50%; spot DES group, n = 89). At 1-year follow-up, 14 patients with full DES (15.6%) and 5 patients (5.6%) with spot DES had a major adverse cardiac event (MACE; p = 0.031). At 3 years, MACEs occurred in 18 patients with full DES (20%) and 7 patients (7.8%) with spot DES (p = 0.019). Cox proportional hazard model showed that the risk for MACEs was almost 60% lower in patients with spot DES compared to those with full DES (hazard ratio 0.41, 95% confidence interval 0.17 to 0.98, p = 0.044). This association remained even after controlling for age, gender, lesion length, and type of stent used (hazard ratio 0.42, 95% confidence interval 0.17 to 1.00, p = 0.05). In conclusion, total lesion coverage with DES is not necessary in the presence of diffuse disease of nonuniform severity. Selective stenting of only the significantly stenosed parts of the lesion is an appropriate therapeutic alternative in this setting, offering a favorable clinical outcome.

Successful percutaneous coronary intervention after implantation of a CoreValve percutaneous aortic valve

BACKGROUND: The association between aortic valve disease and coronary atherosclerosis is common. In the recent era of percutaneous aortic valve replacement (PAVR), there is little experience with coronary artery intervention after valve implantation. CASE REPORT: To our knowledge, this is the first case of successful percutaneous coronary intervention after implantation of a CoreValve percutaneous aortic valve. We report a case of a 79-year-old female patient who underwent successful coronary artery intervention few months after a CoreValve's percutaneous implantation for severe aortic valve stenosis. Verifying the position of the used wires (crossing from inside the self expanding frame) is of utmost importance before proceeding to coronary intervention. In this case, crossing the aortic valve, coronary angiography, and multivessel stenting were successfully performed. CONCLUSION: Percutaneous coronary intervention in patients with previous CoreValve is feasible and safe.

Percutaneous coronary revascularization in patients with formerly "refractory angina pectoris in end-stage coronary artery disease" - not "end-stage" after all

BACKGROUND: Patients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization. METHODS: Thirty-four patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions. RESULTS: Of those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 +/- 42 minutes, range 25-206 minutes) and materials (contrast media 247 +/- 209 ml, range 50-750 ml; PCI guiding wires 2.0 +/- 1.4, range 1-6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1-18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically. CONCLUSION: The majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered.

Surgical versus percutaneous revascularization of coronary artery disease in diabetic patients

Morbidity and mortality related to coronary artery disease (CAD) remain a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. The optimal revascularization strategy continues to evolve due to the advent of new technologies and improved peri-procedural outcome with both percutaneous coronary interventions and coronary artery bypass grafting. Although clinical outcome following coronary artery bypass is worse in diabetic as opposed to non-diabetic patients, surgical revascularization tends to be associated with better outcome in stable patients with multivessel disease and reduced left ventricular function. The advent of drug-eluting stents has challenged the supremacy of coronary artery bypass grafting and has become a valuable alternative to surgery. The safety and efficacy of drug-eluting stents in the treatment of patients with diabetes and multivessel disease is currently under investigation in several ongoing randomized controlled trials. Percutaneous coronary intervention is the therapy of choice in patients with acute coronary syndromes, particularly ST-elevation myocardial infarction. The focus of this review is to present the current evidence, define the role of percutaneous and surgical revascularization in the treatment of diabetic patients with CAD, and propose a tailored approach for clinical decision-making.

Percutaneous left ventricular assist devices during cardiogenic shock and high-risk percutaneous coronary interventions

Left ventricular assist devices were developed to support the function of a failing left ventricle. Owing to recent technological improvements, ventricular assist devices can be placed by percutaneous implantation techniques, which offer the advantage of fast implantation in the setting of acute left ventricular failure. This article reviews the growing evidence supporting the clinical use of left ventricular assist devices. Specifically, we discuss the use of left ventricular assist devices in patients with cardiogenic shock, in patients with acute ST-elevation myocardial infarction without shock, and during high-risk percutaneous coronary interventions.

Myocardial salvage through coronary collateral growth by granulocyte colony-stimulating factor in chronic coronary artery disease: a controlled randomized trial

BACKGROUND: The efficacy of granulocyte colony-stimulating factor (G-CSF) for coronary collateral growth promotion and thus impending myocardial salvage has not been studied so far, to our best knowledge. METHODS AND RESULTS: In 52 patients with chronic stable coronary artery disease, age 62+/-11 years, the effect on a marker of myocardial infarct size (ECG ST segment elevation) and on quantitative collateral function during a 1-minute coronary balloon occlusion was tested in a randomized, placebo-controlled, double-blind fashion. The study protocol before coronary intervention consisted of occlusive surface and intracoronary lead ECG recording as well as collateral flow index (CFI, no unit) measurement in a stenotic and a > or =1 normal coronary artery before and after a 2-week period with subcutaneous G-CSF (10 microg/kg; n=26) or placebo (n=26). The CFI was determined by simultaneous measurement of mean aortic, distal coronary occlusive, and central venous pressure. The ECG ST segment elevation >0.1 mV disappeared significantly more often in response to G-CSF (11/53 vessels; 21%) than to placebo (0/55 vessels; P=0.0005), and simultaneously, CFI changed from 0.121+/-0.087 at baseline to 0.166+/-0.086 at follow-up in the G-CSF group, and from 0.152+/-0.082 to 0.131+/-0.071 in the placebo group (P<0.0001 for interaction of treatment and time). The absolute change in CFI from baseline to follow-up amounted to +0.049+/-0.062 in the G-CSF group and to -0.010+/-0.060 in the placebo group (P<0.0001). CONCLUSIONS: Subcutaneous G-CSF is efficacious during a short-term protocol in improving signs of myocardial salvage by coronary collateral growth promotion.

Coronary artery injury due to catheter ablation in adults: presentations and outcomes

BACKGROUND: Currently, only anecdotal information exists on the presentation and outcome of coronary arterial injury after ablation procedures. METHODS AND RESULTS: Four patients who sustained coronary artery injury of a cohort of patients undergoing 4655 consecutive ablation procedures (0.09%) are described. The patients' mean age was 45+/-11 years, and 1.8+/-0.5 prior ablation attempts had been unsuccessful. Coronary injury occurred from epicardial ventricular tachycardia ablation in 2 patients (irrigated radiofrequency ablation in one and cryoablation in the other) and ablation within the middle cardiac vein with irrigated radiofrequency in 2 patients. All involved branches of the right coronary artery. Acute occlusion presenting with ST-segment elevation immediately after ablation was recognized during the procedure in 2 cases. Occlusion failed to respond to nitroglycerin or balloon dilation, and stenting was required in both cases. Acute myocardial infarction occurred 2 weeks after epicardial ablation as a result of occlusion of a right ventricular branch of the right coronary artery giving rise to the posterior descending coronary artery in 1 patient. A moderate asymptomatic stenosis was seen on angiography after epicardial cryoablation in 1 patient. All patients recovered and remained asymptomatic from the coronary injury and arrhythmias during 37+/-53 months of follow-up. CONCLUSIONS: Coronary arterial injury after ablation procedures is rare. It may present acutely or several weeks after an ablation procedure. Acute occlusion appears to require coronary stenting. Unanticipated anatomic variations can predispose to coronary injury.